title: Dual thermoresponsive and pH-responsive self-assembled micellar nanogel for anticancer drug delivery.
abstract: In this article, we prepared a dual thermoresponsive and pH-responsive self-assembled micellar nanogel for anticancer drug delivery by using a degradable pH-responsive ketal derivative, mPEG2000-Isopropylideneglycerol (mPEG-IS, PI) polymer. The purpose of this study is to develop an injectable dual-responsive micellar nanogel system which has a sol-gel phase transition by the stimulation of body temperature with improved stability and biocompatibility as a controlled drug delivery carrier for cancer therapy. The pH-responsive PI was designed with pH-responsive ketal group as hydrophobic moieties and PEG group as hydrophilic moieties. The PI micelles encapsulated paclitaxel (PTX) was fabricated. Then, the PI micelles were formed in a thermo-nanogel. The micellar nanogel could improve the solubility and stability of PTX. The physiochemical properties of PI micelles and micellar nanogel were characterized. The results showed that dual-responsive micellar nanogel could carry out sol-gel transition at 37 °C. The PI polymer can spontaneously self-assemble into micellar structure with size of 100-200 nm. The dual-responsive micellar nanogel could be degraded under lower pH condition. The test in vitro PTX release showed that dual-responsive micellar nanogel could release about 70% for 70 h under pH 5.0 while about 10% release at pH 7.4 and pH 9.0. The dual-responsive micellar nanogel was of lower cytotoxicity and suppressed tumor growth most efficiently. The micellar nanogel will be a new potential dual-responsive drug delivery system for cancer therapy.
authors.affiliation: School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Daquan
authors.initials: D
authors.lastname: Chen
authors.forename: Hongyun
authors.initials: H
authors.lastname: Yu
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D000080385:Nanogels; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D017239:Paclitaxel
keywords: Micellar nanogel; PTX delivery; mPEG-IS (PI); pH-responsive micelles; thermoresponsive